AUSTRALIAN PRODUCT INFORMATION NEUPRO® (ROTIGOTINE) TRANSDERMAL PATCHES 1 NAME OF THE MEDICINE Rotigotine 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Neupro 1 mg: 5 cm2 patch containing 2.25 mg rotigotine with a nominal release rate of 1 mg rotigotine per 24 hours. Neupro 2 mg: 10 cm2 patch containing 4.5 mg rotigotine with a nominal release rate of 2 mg rotigotine per 24 hours. Neupro 3 mg: 15 cm2 patch containing 6.75 mg rotigotine with a nominal release rate of 3 mg rotigotine per 24 hours. Neupro 4 mg: 20 cm2 patch containing 9.0 mg rotigotine with a nominal release rate of 4 mg rotigotine per 24 hours. Neupro 6 mg: 30 cm2 patch containing 13.5 mg rotigotine with a nominal release rate of 6 mg rotigotine per 24 hours. Neupro 8 mg: 40 cm2 patch containing 18.0 mg rotigotine with a nominal release rate of 8 mg rotigotine per 24 hours. The active ingredient rotigotine is a white to light brownish powder. It is very slightly soluble to freely soluble in organic solvents, sparingly soluble in acidic aqueous solutions and practically insoluble in alkaline aqueous solutions. The formulation contains sodium metabisulfite. For the full list of excipients, see Section 6.1 List of Excipients. 3 PHARMACEUTICAL FORM Neupro is a thin, matrix-type transdermal patch composed of 3 layers: 1. A flexible, tan-colored backfilm that provides structural support and protection of the drug loaded adhesive layer. 2. A self-adhesive drug matrix layer. 3. A clear protective liner which is removed prior to use. Thin, matrix type transdermal patch that is square shaped with rounded edges. The backing layer comprises a polyester film, siliconized, aluminized, colour coated with a tan coloured pigment (titanium dioxide (E171), pigment yellow 95, pigment red 166) layer and imprinted (pigment red 144, pigment yellow 95, pigment black 7). The protective liner comprises a transparent fluoropolymer coated polyester film. The outside of the tan coloured backing layer is imprinted with Neupro 1 mg/24 h, Neupro 2 mg/24 h, Neupro 3 mg/24 h, Neupro 4 mg/24 h, Neupro 6 mg/24 h or Neupro 8 mg/24 h respectively. Page 1 4 CLINICAL PARTICULARS 4.1 THERAPEUTIC INDICATIONS Parkinson's disease Neupro is indicated as monotherapy, or in combination with levodopa, for the treatment of idiopathic Parkinson's disease from early stage to advanced disease. Restless legs syndrome Neupro is indicated for the symptomatic treatment of moderate to severe idiopathic restless legs syndrome in adults. 4.2 DOSE AND METHOD OF ADMINISTRATION Neupro is applied once a day. The patch should be applied at approximately the same time every day. The patch remains on the skin for 24 hours and will then be replaced by a new one at a different site of application. If the patient forgets to apply the patch at the usual time of the day or if the patch becomes detached, another patch should be applied for the remainder of the day. Neupro can be applied irrespective of the timing of meals. Dosage The dose recommendations made below are in nominal dose. Parkinson's disease Dosing in patients with early stage Parkinson's disease A single daily dose should be initiated at 2 mg/24 h and then increased in weekly increments of 2 mg/24 h to an effective dose up to a maximal dose of 8 mg/24 h. 4 mg/24 h may be an effective dose in some patients. For most patients an effective dose is reached within 3 or 4 weeks at doses of 6 mg/24 h or 8 mg/24 h, respectively. The maximal dose is 8 mg/24 h. Dosing in patients with advanced stage Parkinson's disease A single daily dose should be initiated at 4 mg/24 h and then increased in weekly increments of 2 mg/24 h to an effective dose up to a maximal dose of 16 mg/24 h. 4 mg/24 h or 6 mg/24 h may be effective doses in some patients. For most patients an effective dose is reached within 3 to 7 weeks at doses of 8 up to a maximum dose of 16 mg/24 h. For doses higher than 8 mg/24 h multiple patches may be used to achieve the final dose, e.g. 10 mg/24 h may be reached by combination of a 6 mg/24 h and a 4 mg/24 h patch. Restless legs syndrome A single daily dose should be initiated at 1 mg/24 h. Depending on the individual patient response, the dose may be increased in weekly increments of 1 mg/24 h to a maximal dose of 3 mg/24 h. The need for treatment continuation should be reconsidered every 6 months for risk/benefit analysis. Page 2 Special populations Hepatic and renal impairment Adjustment of the dose is not necessary in patients with mild to moderate hepatic impairment or in patients with mild to severe renal impairment including those requiring dialysis (see Section 4.4 Special Warnings and Precautions for Use and Section 5.2 Pharmacokinetic Properties). Rotigotine has not been investigated in patients with severe hepatic impairment. Children and adolescents Rotigotine is not recommended for use in children and adolescents due to a lack of data on safety and efficacy. Treatment discontinuation Parkinson's disease Neupro should be discontinued gradually. The daily dose should be reduced in steps of 2 mg/24 h with a dose reduction preferably every other day, until complete withdrawal of Neupro (see Section 4.4 Special Warnings and Precautions for Use). Restless legs syndrome Neupro should be discontinued gradually. The daily dose should be reduced in steps of 1 mg/24 h with a dose reduction preferably every other day, until complete withdrawal of Neupro (see Section 4.4 Special Warnings and Precautions for Use). Following this procedure, rebound (worsening of symptoms beyond initial intensity after discontinuation of treatment) was not observed. Method of administration The patch should be applied to clean, dry, intact healthy skin on the abdomen, thigh, hip, flank, shoulder or upper arm. Reapplication to the same site within 14 days should be avoided. Neupro should not be placed on skin that is red, irritated or damaged (see Section 4.4 Special Warnings and Precautions for Use). Use and handling Each patch is packed in a sachet and should be applied directly after the sachet has been opened. One half of the protective liner should be removed and the sticky side should be applied and pressed firmly to the skin. Then, the patch is folded back and the second part of the protective liner is removed. The sticky side of the patch should not be touched. The patch should be pressed down firmly with the palm of the hand for about 20-30 seconds, so that it sticks well. Neupro does not need to be removed for bathing or swimming. In the event that a patch becomes detached, a new patch should be applied for the remainder of the 24 hour dosing interval. The patch should not be cut into pieces. 4.3 CONTRAINDICATIONS Hypersensitivity to the active substance or to any of the excipients. Magnetic resonance imaging or cardioversion (see Section 4.4 Special Warnings and Precautions for Use). Page 3 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE Magnetic resonance imaging and cardioversion The backing layer of Neupro contains aluminium. To avoid skin burns, Neupro should be removed if the patient has to undergo magnetic resonance imaging (MRI) or cardioversion. Orthostatic hypotension Dopamine agonists are known to impair the systemic regulation of the blood pressure resulting in postural/orthostatic hypotension. These events were also observed during treatment with Neupro, however, the incidence was similar to that in placebo treated patients. It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of orthostatic hypotension associated with dopaminergic therapy. Elevation of blood pressure and heart rate Some patients treated with Neupro exhibited increases in systolic blood pressure (greater than 180 mmHg) and/or diastolic blood pressure (greater than 105 mmHg) while supine or standing. Some patients treated with Neupro exhibited increased pulse (greater than 100 beats per minute) while supine and/or standing. These findings of blood pressure and heart rate elevations should be considered when treating patients with cardiovascular disease. Syncope Syncope was observed in association with rotigotine, but also at a similar rate in patients treated with placebo. Patients with severe cardiovascular disease should be asked about symptoms of syncope and pre-syncope. Somnolence and sudden onset of sleep Patients treated with Neupro have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence while on Neupro, some perceived no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events have been reported as late as one year after initiation of treatment. Somnolence is a common occurrence in patients receiving Neupro. Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing somnolence, although patients may not give such a history. For this reason, prescribers should continually reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Patients should be advised to exercise caution while driving, operating machines, or working at heights during treatment with Neupro.